Granulomas are a frequent challenge for pathologists, which can be identified both in histological and cytological material in a number of conditions. With regard to interstitial lung diseases, granulomas can be associated with infection (e.g. mycobacterial), immunological conditions (e.g. hypersensitivity pneumonitis), or may be idiopathic (e.g. sarcoidosis). Considering morphology, features that should be identified are the presence of necrosis, the cohesiveness and coalescence of granulomas, the presence of fibrosis and the amount and quality of the associated inflammatory infiltrate. The most interesting approach to granulomatous lung disease is indeed represented by their pattern of distribution within the secondary lobule; in fact, granulomas can be distributed along lymphatic routes (e.g. sarcoidosis), randomly (miliary infections, e.g. mycobacterial and fungal infections), or along the airways (hypersensitivity pneumonitis, hot tub lung, aspiration pneumonia and sometimes infections). We propose a combined radiological-histopathological approach for defining the morphological features and anatomic localization of granulomatous ILDs. In addition, a detailed review of their clinical features is provided, together with a description of the main procedures used to obtain respiratory samples for pathology and microbiology studies in these patients.